The complete molecular mechanism responsible for olfaction has yet to be elucidated. However, odorant binding activity has been detected in mammalian olfactory tissue extracts. In addition, behavioral and neurophysiological evidence suggests the existence of specific olfactory receptor proteins. For example, Amoore reports losses of the sense of smell (anosmias) to about thirty discrete odorant groups. (Chem. Senses Flavor, Vol. 2, pp. 267-281, 1977.) In addition, there is evidence for a binding protein for urinous odorants (Persaud et al, in Biochemistry of Taste and Olfaction (1981), Cagan et al, editors, pp. 333-357, Academic Press, New York), a camphor-binding protein (Fesenko et al, Biochim. Biophys. Acta, Vol. 587, pp. 424-433, 1979) and a binding protein for green smelling odorants such as 2-isobutyl-3-methoxyprazine (IBMP) (Pelosi et al, Biochemical Journal, Vol. 201, pp. 245-248, 1982). Despite these findings, the molecular identity of most of the components of the olfactory system remain undefined.
At the molecular level, several proteins have been identified which appear to be involved in olfaction. Lee et al, Science, Vol. 235, pp. 1053-1956 (1987) report the isolation of an olfactory cDNA from the frog. The mRNA corresponding to the isolated cDNA appears to be abundant in the Bowman's glands in olfactory tissue, but not in other tissues tested. Although the function of the protein encoded by the gene is unknown, its sequence shares homology with members of a family of proteins that bind and transport small molecules in the serum, suggesting a transporting role for this protein.
Another protein presumably involved in olfaction is the so-called pyrazine-binding protein or odorant-binding protein from cow nasal tissue. This protein was first detected on the basis of its binding activity for "green" smelling compounds such as 2-isobutyl-3-methoxypyrazine. (See Bignetti et al, European Journal of Biochemistry, Vol. 149, pp. 227-231, 1985 and Pevsner et al, Proceedings of the National Academy of Sciences, Vol. 82, pp. 3050-3054, 1985.) This cow protein has been purified to apparent homogeneity and a partial amino acid sequence has been determined (See Cavaggioni et al, FEBS Letters, Vol. 212, pp. 225-228, 1987). Homology between this cow protein and the major mouse urinary proteins (MUP) and the rat alpha-2-microglobulins (AMG) was noted.
A rat odorant-binding protein has also been purified to apparent homogeneity. (Pevsner et al, Proceedings of the National Academy of Sciences U.S.A., Vol. 83, pp. 4942-4946, 1986.) The protein was found in both olfactory and respiratory epithelium. Although it was known that the rat odorant protein was secreted into the nasal mucus and tears, it was not known where this protein was synthesized.
Another identified protein which is presumably involved in olfaction is the so-called olfactory marker protein (OMP). This is a neuronal gene product which is developmentally regulated and whose expression is restricted to mature olfactory receptor neurons of many vertebrate species. The gene for this protein has been cloned and sequenced. (See Rogers et al, Proceedings of the National Academy of Sciences U.S.A., Vol. 84, pp. 1704-1708, 1987.) Another protein which has been identified in the olfactory perception system is an odorant-sensitive adenylate cyclase. This was found in olfactory sensory neurons and requires the presence of guanosine triphosphate (GTP). Only certain odorants are found to stimulate the enzyme activity. (See Journal of Biological Chemistry, Vol. 61, pp. 15538-15543, 1986.)
There is a need for a more thorough understanding of the components of the olfactory perception system. Molecular cloning of these components can facilitate the understanding of the mechanism of olfaction by allowing the production of large amounts of the individual components. Further, molecular cloning can facilitate the determination of the sites of synthesis of various components of the olfactory system.
Because odorant molecules are often present in rather small amounts in natural sources, they can be difficult to isolate and/or analyze. Thus there is a need for a large source of an odorant binder to facilitate the isolation and identification of odorant molecules. Further, some odorant molecules are readily absorbed into the skin which can both be deleterious to the health and cause the odorant (for example, a perfume) to have a short active life on the skin. Therefore there is a need in the art for compounds which can extend the active life of odorants on the skin. In addition, many odorants are lipophilic, and thus are difficult to bring into aqueous or semi-aqueous solution. Thus there is a need in the art for compounds which can facilitate the emulsification of lipophilic odorant molecules.